Susceptibility of autologous target cells to lysis by lymphokine-activated effectors from interferon-alpha-treated chronic myelogenous leukaemia patients.
Chronic myelogenous leukemia (CML) patients in chronic phase display compromised lymphokine-activated killer (LAK) cell induction, which is partly restored after therapy with interferon alpha. However, the relative resistance of the leukemic cells from these patients to autologous or allogeneic LAK lysis is not affected by this treatment. In an attempt to render CML cells more susceptible to lysis or cytostasis, they were precultured in serum-free medium with or without recombinant growth factors. In eight patients studied, interleukin-3 (IL-3) significantly enhanced the spontaneous short-term (6-day) proliferation of CML cells, with retention of ability to form colonies in methylcellulose. Culture in either medium alone or IL-3 led to a significant enrichment of CD14+ and CD33+ cells but to a reduction in CD34+ cells. In contrast, culture of the same cells in IL-2 (to generate autologous LAK activity) resulted in a loss of CD14+ and CD33+ as well as CD34+ cells but in a significant increase in CD3+ and CD56+ cells. Despite similarities in their phenotypes, IL-3 cultured cells but not those cultured in medium alone acquired susceptibility to lysis by the IL-2-cultured autologous LAK cells. These results may have significance for the design of novel combination immunotherapy in CML.
Pawelec
G
G
Second Department of Internal Medicine, University Medical Clinic, Tübingen, Federal Republic of Germany.
Ehninger
G
G
Schmidt
H
H
Müller
C
C
Bühring
H J
HJ
Reutter
M
M
Busch
F W
FW
D000954:Antigens, Surface / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology* / Q000627:therapeutic use; D007377:Interleukin-3 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000473:pathology; D010641:Phenotype; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D016207:Cytokines; D007370:Interferon Type I; D007377:Interleukin-3